Long-term trajectories of bone metabolism parameters and bone mineral density (BMD) in obese patients treated with metabolic surgery: a real-world, retrospective study.

PURPOSE: Potential negative effects of metabolic surgery on skeletal integrity remain a concern, since long-term data of different surgical approaches are poor. This study aimed to describe changes in bone metabolism in subjects with obesity undergoing both Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). METHODS: A single center, retrospective, observational clinical study on real-world data was performed enrolling subjects undergoing metabolic surgery. RESULTS: 123 subjects were enrolled (males 31: females 92; ages 48.2 ± 7.9 years). All patients were evaluated until 16.9 ± 8.1 months after surgery, while a small group was evaluated up to 4.5 years. All patients were treated after surgery with calcium and vitamin D integration. Both calcium and phosphate serum levels significantly increased after metabolic surgery and remained stable during follow-up. These trends did not differ between RYGB and SG (p = 0.245). Ca/P ratio decreased after surgery compared to baseline (p < 0.001) and this decrease remained among follow-up visits. While 24-h urinary calcium remained stable across all visits, 24-h urinary phosphate showed lower levels after surgery (p = 0.014), also according to surgery technique. Parathyroid hormone decreased (p < 0.001) and both vitamin D (p < 0.001) and C-terminal telopeptide of type I collagen (p = 0.001) increased after surgery. CONCLUSION: We demonstrated that calcium and phosphorous metabolism shows slight modification even after several years since metabolic surgery, irrespective of calcium and vitamin D supplementation. This different set point is characterized by a phosphate serum levels increase, together with a persistent bone loss, suggesting that supplementation alone may not ensure the maintenance of bone health in these patients.

The hypothalamic-pituitary-adrenal and -thyroid axes activation lasting one year after an earthquake swarm: results from a big data analysis.

PURPOSE: To cope physical and/or psychological threats, the human body activates multiple processes, mediated by a close interconnection among brain, endocrine and inflammatory systems. The aim of the study was to assess the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axes involvement after an acute stressful event (Emilia Romagna earthquake swarm) with a big data approach. METHODS: A retrospective, observational trial was performed, collecting all biochemical examinations regarding HPA and HPT axes performed in the same laboratory the year before and the year after the earthquake swarm (20-29 May 2012). RESULTS: Comparing 2576 pre-earthquake to 3021 post-earthquake measurements, a cortisol serum level increase was observed (p < 0.001). Similar increase was evident for urinary free cortisol (p = 0.016), but not for adrenocorticotropic hormone (p = 0.222). The biochemical hypercortisolism incidence increased from 7.6 to 10.3% after earthquakes (p = 0.001). Comparing 68,456 pre-earthquake to 116,521 post-earthquake measurements, a reduction in thyroid-stimulating hormone (TSH) levels was evident (p = 0.018), together with an increase in free triiodothyronine and free thyroxine levels (p < 0.001 and p < 0.001). Moreover, a significant increase in altered TSH after earthquakes was registered considering the epicenter-nearest measurements (p < 0.001). No clinically relevant alterations were observed considering thyroid-specific autoantibodies. CONCLUSION: A long-term HPA axis activation in the inhabitants of the earthquake-affected areas was highlighted for the first time. Moreover, an increased incidence of biochemical hypercortisolism emerged after earthquakes. We confirmed a recruitment of HPT axis after stressful events, together with increased incidence of altered TSH in the. Our big data study allowed to increase knowledge about the connection between external stressors and endocrine regulation.

Multi-strain yeast fraction product supplementation can alleviate weaning stress and improve performance and health of piglets raised under low sanitary conditions.

BACKGROUND: This study was conducted to evaluate the health benefits to weaning pigs, raised under low sanitary conditions, of dietary supplementation with a multi-strain yeast fraction product (Cyberlindnera jadinii and Saccharomyces cerevisiae). In total, 160 weaning pigs (7.21 ± 1.05 kg) were randomly allotted to two dietary treatments in a 6-week feeding trial. The dietary treatments included a corn-soybean meal-based basal diet (CON) and CON + 2 g kg-1 multi-strain yeast fraction product (MsYF) during weeks 1-2 and 0.4 g kg-1 MsYF during weeks 3-6. RESULTS: The MsYF supplementation increased (P < 0.05) body weight (BW) at day 42 and average daily gain (ADG) during days 1-14 and days 1-42 (P < 0.05) compared to CON. The total tract digestibility of dry matter (DM), fecal Lactobacillus counts, and serum immunoglobulin G (IgG) concentration at day 42 were higher (P < 0.05) in pigs fed a MsYF supplemented diet. The concentration of serum haptoglobin in pigs receiving a MsYF-supplemented diet was higher (P < 0.05) at days 7, 14, and 42 than those receiving CON. The mRNA expression for INF-γ and TNF-α genes were lower (P < 0.05) at days 14 and 7 respectively and the expression of IL-6 and TLR-2 genes was lower (P < 0.01) at days 7 and 14 in pigs fed an MsFY supplemented diet than those fed CON. CONCLUSION: Supplementation with a multi-strain yeast fraction product had a positive effect on ADG during the early post-weaning period and led to better health in weaning pigs. © 2019 Society of Chemical Industry.

Effects of cellulase supplementation to corn soybean meal-based diet on the performance of sows and their piglets.

A total of 15 primiparous sows (Landrace × Yorkshire) and their litters were used in the current study to evaluate the efficacy of cellulase supplementation on the production performance of sows and piglets. Pigs were randomly allocated into one of three treatments with five replicates per treatment. The dietary treatments were as follows: (i) CON (corn-soybean meal-based control); (ii) EZ1 (CON + 0.05% cellulase); and (iii) EZ2 (CON + 0.10% cellulase). The supplementation of cellulase had no effect (P > 0.05) on body weight and feed intake of lactating sows. At weaning, back fat thickness loss decreased (P = 0.04) linearly in EZ1 and EZ2 treatments. The average daily gain (ADG) of piglets increased (linear P = 0.06, quadratic P = 0.04)) during days 14 to 21 as well as at days 21 to 25 (linear P = 0.03 and quadratic P = 0.01) with the increase in the level of supplemented enzyme. Dry matter and nitrogen digestibility increased (linear P = 0.01) in lactating sows fed EZ1 and EZ2 diet compared with CON. In conclusion, it is suggested that cellulase supplementation to corn-soybean meal based diet exerts beneficial effects to sows in reducing their back fat thickness loss at weaning and also helps to improve nutrient digestibility. It also helped to improve the ADG of piglets.

Outcomes of androgen replacement therapy in adult male hypogonadism: recommendations from the Italian society of endocrinology.

OBJECTIVE: We developed clinical practice guidelines to assess the individual risk-benefit profile of androgen replacement therapy in adult male hypogonadism (HG), defined by the presence of specific signs and symptoms and serum testosterone (T) below 12 nmol/L. PARTICIPANTS: The task force consisted of eight clinicians experienced in treating HG, selected by the Italian Society of Endocrinology (SIE). The authors received no corporate funding or remuneration. CONSENSUS PROCESS: Consensus was guided by a systematic review of controlled trials conducted on men with a mean T < 12 nmol/L and by interactive discussions. The guidelines were reviewed and sequentially approved by the SIE Guidelines Commission and Executive Committee. CONCLUSIONS: We recommend T supplementation (TS) for adult men with severely reduced T levels (T < 8 nmol/L) to improve body composition and sexual function. We suggest that TS be offered to subjects with T < 12 nmol/L to improve glycaemic control, lipid profile, sexual function, bone mineral density, muscle mass and depressive symptoms, once major contraindications have been ruled out. We suggest that lifestyle changes and other available interventions (e.g. for erectile dysfunction) be suggested prior to TS. We suggest that TS should be combined with currently available treatments for individuals at high risk for complications, such as those with osteoporosis and/or metabolic disorders. We recommend against using TS to improve cardiac outcome and limited mobility. We recommend against using TS in men with prostate cancer, unstable cardiovascular conditions or elevated haematocrit. The task force places a high value on the timely treatment of younger and middle-aged subjects to prevent the long-term consequences of hypoandrogenism.

Flavonol glycosides found in hydroethanolic extracts from Tilia cordata, a species utilized as anxiolytics / Flavonóides glicosídeos encontrados no extrato hidroalcoólico de Tilia cordata, espécie usada como ansiolítico

Tilia species, among which is Tilia cordata Mill. (Tiliaceae), have been used in folk medicine as anxiolytic. The hydroethanolic extract was analyzed by using liquid chromatography with mass spectrometry HPLC-DAD-ESI-MS/MS in negative ion mode, and its chemical composition was compared to flavonoids reported as anxiolytics. The major flavonoids found were: quercetin-3,7-di-O-rhamnoside, kaempferol-3,7-di-O-rhamnoside and kaempferol 3-O-(6"-p-coumaroyl glucoside) or tiliroside. The anxiolytic activity of the genus Tilia has been attributed to the presence of quercetin and kaempferol derivatives, while the anxiolytic activity of T. americana var. Mexicana was attributed to tiliroside, which was also found among the major constituents of this species.

As espécies de Tilia, entre elas, a Tilia cordata Mill. (Tiliaceae) são utilizadas como ansiolíticas na medicina popular. O extrato hidroalcoólico foi analisado usando cromatografia líquida acoplada à espectrometria de massas HPLC-DAD-ESI/MS/MS no modo negativo e a sua composição química foi comparada com os flavonóides já reportados como ansiolíticos. Os principais flavonóides encontrados foram: quercetina-3,7-di-O-rhamnosideo, canferol-3,7-di-O-rhamnosideo, e canferol 3-O-(6"-p-cumaroil glucosideo) ou tilirosideo. A atividade ansiolítica do gênero Tília tem sido atribuída à presença de derivados de canferol e quercetina, enquanto que a atividade ansiolítica da T. americana var. Mexicana foi atribuída ao tilirosideo, o qual também foi encontrado entre os principais constituintes desta espécie.

Development and screening of a polyketide virtual library for drug leads against a motilide pharmacophore.

A virtual library of macrocyclic polyketide molecules was generated and screened to identify novel, conformationally constrained potential motilin receptor agonists ("motilides"). A motilide pharmacophore model was generated from the potent 6,9-enol ether erythromycin and known derivatives from the literature. The pharmacophore for each molecular conformation was a point in a distance-volume space based on presentation of the putative binding moieties. Two methods, one fragment based method and the other reaction based, were explored for constructing the polyketide virtual library. First, a virtual library was assembled from monomeric fragments using the CHORTLES language. Second, the virtual library was assembled by the in silico application of all possible polyketide synthase enzyme reactions to generate the product library. Each library was converted to low-energy 3D conformations by distance geometry and standard minimization methods. The distance-volume metric was calculated for low-energy conformations of the members of the virtual polyketide library and screened against the enol ether pharmacophore. The goal was to identify novel macrocycles that satisfy the pharmacophore. We identified three conformationally constrained, novel polyketide series that have low-energy conformations satisfying the distance-volume constraints of the motilide pharmacophore.

Selective killing of transformed cells by methotrexate with histidine deprivation or with alpha-amino alcohols.

The effects of amino acid deprivation and treatment with amino alcohols upon the growth, viability, and susceptibility to methotrexate (MTX) cytotoxicity were examined in BALB/3T3 cells and their virally transformed counterparts, SV-T2 cells. Cells were deprived of either histidine or tyrosine plus phenylalanine, or they were treated with amino alcohol analogues of histidine and tyrosine (histidinol and tyrosinol). When incubated in medium lacking histidine and supplemented with dialyzed serum (histidine-deficient medium), the BALB/3T3 cells remained viable for at least 3 days, but they ceased logarithmic growth, and the cell number reached an early plateau. In contrast, the SV-T2 cells continued to divide in histidine-deficient medium. Neither cell line ceased division in medium deficient in both phenylalanine and tyrosine. Incubation of the BALB/3T3 cells with 1.5 mM histidinol or 1.0 mM tyrosinol caused an early plateau similar to the effect of histidine deprivation. SV-T2 cells were not affected by these concentrations of histidinol or tyrosinol, but growth was arrested at higher concentrations. Any of the conditions used which caused a plateau in the number of BALB/3T3 cells substantially protected the treated cells from cell death caused by MTX. Therefore, pretreatment of BALB/3T3 cells with histidine deprivation, 1.5 mM histidinol, or 1.0 mM tyrosinol protected this cell line against MTX-induced cell death, while the same pretreatment conditions failed to protect SV-T2 cells. (SV-T2 cells were protected by 4.0 mM histidinol.) Thus, the ability of MTX to kill cells in vitro can be selectively modified by conditions which protect cells which retain normal growth control characteristics, but which do not protect virally transformed cells.